A challenge in the design of anti-cancer therapeutic drugs is the general toxicity of such drugs to proliferating cells, including a percentage of normal cells. A ubiquitous class of anti-cancer therapeutics includes compounds that modify, bind to, and inhibit the synthesis of DNA. This class lacks selectivity, leading to high levels of intolerable side effects stemming from the modification or interaction of DNA in non-cancerous, highly replicating cells. Such off-target effects limit tolerated doses and, hence, decreases efficacy.
Various strategies are currently under development with the goal of enhancing chemotherapy selectivity for cancer cells. For example, one strategy involves attaching therapeutic agents to active transport scaffolds such that bio-distribution of the therapeutic agent is selective for cancer cells. Other approaches involve antibody use, nanoparticles, enzymatic activation, and the like.
Many forms of cancer, and in particular ROS-associated cancers, have low survival rates, primarily due to high relapse rates. For example, in the United States, 44,600 new cases of leukemia, a ROS-associated cancer, were diagnosed in 2011, with a five-year survival rate of 57%. One of the deadliest forms of leukemia, acute myeloid leukemia (AML), accounted for 12,950 of those cases and 9,050 deaths.
A need remains for additional anti-cancer therapeutics, particularly those which target cancer cells with higher selectivity.